Chapter 11: Gene Expression Control in Division & Development pp 217-228 Prokaryotes • 1965 Nobel Prize to Jacob & Monod for work on lac operon in E. coli • Lactose is metabolized by 3 enzymes in E. coli • Genes for these proteins are sequential • An operator sits between promoter & these structural genes • lac operon = promoter + operator + 3 genes • Upstream regulatory gene codes for repressor lac operon http://www.sumanasinc.com/webcontent/animations/biology.html lac operon http://www.phschool.com/science/biology_place/biocoach/lacoperon/ regulate.html How it works. • Regulatory gene codes for repressor protein • Repressor protein binds to the operator site • Repressor prevents RNA polymerase advancement from its promoter site • Repressor protein selectively binds lactose & cannot bind the operator site then • Repression is lifted genes are “turned on” only when lactose is present Eukaryotic control • Control is at level of individual chromosome • Euchromatin, uncoiled DNA, is site of active transcription • DNA contains bases that code for proteins (exons) & bases that do not (introns) • Exons & introns are both transcribed • Only exons are translated • Introns may serve as regulatory elements Transcriptional Control • Pre-mRNA is full copy of DNA gene’s message • Splicesomes (RNA + protein) cut out introns & fuse exons; ribozymes (RNA) also splice • Introns regulate RNA, bind to &/ or control expression • Exons can code for functional domains • Exons can be selected to form specific protein Transcriptional Control • Transcription factors (TF) bind to regulatory elements on DNA, proteins, & other TF – Promoters – Enhancers – Repressors • TF recruit RNA polymerase to promoter • TF-to-TF binding can change shape of DNA TF-binding Interactions Genes for Development • Cells differentiate to become specialized – Every zygote has all the DNA – Cells/ tissue specialize in morphogenesis – Cells only express DNA for their functions • Homeotic genes dictate loci of anatomy – Specific sequence within gene = “homeobox” • Homeotic genes form regulatory proteins – Control which genes are expressed – Control rates of cell division & gene expression Cancer & Cell Control • Proto-oncogenes control normal cell division, growth, & behavior • Carcinogen = mutagen DNA damage • Mutated proto-oncogenes “oncogene” • Oncogenes promote uncontrolled growth tumors (benign or malignant) cancer • Metastasis = spread of CA beyond origin • Mutated tumor-suppressor genes cancer – Mutations in all 3 tumor-suppressor genes + viral oncogene + mutated proto-oncogene Types of Cancer • Carcinomas – Skin & tissues lining organs • Sarcomas – Bone & muscle • Lymphomas – Lymphatic system’s solid tumors • Leukemia – Blood-forming tissues uncontrolled WBC production